Browsing by Author "Bettencourt, A. F."
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- Evaluation of a dual function minocycline polymeric bone scaffoldPublication . Anjos, I.; Zegre, Miguel; Santos, C.; Alves, M. M.; Ribeiro, I.; Gonçalves, L.; Bettencourt, A. F.It is estimated that orthopedic procedures will rise due to population growth along with aging and increasing chronic diseases. Consequently, orthopedic infections associated with these procedures can be a serious complication, leading to a state of morbidity. Current strategies for treating bone infections and defects present several limitations, namely low local concentrations and systemic toxicity. To overcome these limitations, synthetic and biocompatible bone grafts substitutes (scaffolds) are being developed as platforms for local drug delivery, a strategy that allows high antibiotics concentration in bone for orthopedic infections treatment. Thus, this work aims to develop a drug delivery system with osteoconductive and osteoinductive properties for bone regeneration and capable of treating the infection. For this purpose, porous PDLLA scaffolds were produced by the solvent casting technique, functionalized with bioglass (BG) and collagen (Col), and loaded with 0.5, 0.25, 0.1, or 0.05 mg/mL of minocycline hydrochloride (MH), a dual function drug that beyond its antibiotic role, also induce osteoblastic cells differentiation. Scaffolds’ surface morphology was characterized by scanning electron microscopy (SEM) and elemental chemical composition was performed by X-ray energy dispersive spectrometer (EDS). These drug delivery systems were also characterized in terms of drug release profiles and cytocompatibility through in vitro studies. SEM analysis demonstrated a porous surface and confirmed the functionalization. Regarding drug release profiles, the obtained results suggest a two-phase stage release, with an initial burst release of approximately 60%, 30%, and 10% of MH in the first 15 min, for the two most MH concentrated groups, 0.1 mg/mL of MH group and 0.05 mg/mL of MH group, respectively, followed by a sustained release. In vitro cell studies were promising for scaffolds adsorbed with 0.1 and 0.05 mg/mL of MH, not revealing cytotoxicity, contrary to what was seen for scaffolds with higher concentrations of MH (0.5 and 0.25 mg/mL).In conclusion, due to release profiles of the drug and in vitro cell assays, scaffolds adsorbed with the two lowest MH concentrations seem a promising strategy for acute infection treatment, however, antimicrobial assays must be conducted.
- In vitro cytocompatibility evaluation of poly(DL-lactic acid) scaffolds loaded with minocycline and voriconazole addressing osteomyelitisPublication . Zegre, Miguel; Caetano, Liliana Aranha; Gonçalves, L. M.; Bettencourt, A. F.Osteomyelitis or bone infection is an acute or chronic inflammatory process involving the bone and its structures, secondary to infection with pyogenic organisms, such as bacteria and fungi. Considering the associated high patient economic burden, morbidity, and mortality, it is essential to develop novel strategies for osteomyelitis management. Porous scaffolds based on biomaterials may locally deliver high concentrations of antibiotics, an effective strategy in eradicating bone infection. When incorporating bioactive bioglasses and bioresorbable polymers like poly(DL-lactic acid) (PDLLA), these structures exhibit biosafety, biodegradability, and the expected global structure to promote cell expansion and cell differentiation, being critical to consider and evaluate their biocompatibility compliance. As the encapsulation of more than one active pharmaceutical ingredient is an attractive approach, the present study focuses on the cytocompatibility evaluation of an innovative system based on the dual delivery of two antimicrobials, an antibiotic that enhances bone formation, minocycline (MH), and an antifungal agent with a broad spectrum of activity, voriconazole (VCZ), aiming bone infection therapeutics. Scaffolds were prepared by solvent casting/particulate leaching techniques and functionalized with bioglass. The scaffolds produced were adsorbed with 0.5 or 0.1 mg/mL of minocycline and also with 0.1 mg/mL of voriconazole. To test the bio-functionality and the biological safety of scaffolds, in vitro cell assays were achieved employing the MG-63 cell line (ATCC® CRL-1427TM human osteoblast cell line). The AlamarBlue® assay was used to measure cell proliferation in the scaffold. As osteoblast differentiation markers, the following were determined: alkaline phosphatase activity and mineralization using Alizarin red assay, an indicator of in vitro bone formation. All scaffolds sustained the proliferation of metabolically active cells, nonetheless, scaffolds adsorbed with the highest concentration of MH (0.5 mg/mL) presented a significant (p<0.05) cytotoxic effect. Matrix maturation assays supported early osteoblasts differentiation and the osteoinductive role of minocycline described in the literature was also highlighted. Matrix mineralization analysis showed the highest value associated with scaffolds with both antimicrobials adsorbed. Once the described scaffolds enhanced osteoblasts' differentiation, and matrix mineralization and evidenced no cytotoxic effects, they come to light as an auspicious alternative for local antimicrobial therapy addressing osteomyelitis prevention and therapeutics.